Insight into Failing Heart Cells

Insight into Failing Heart Cells

The new technique used in the study is called scanning ion conductance microscopy (SICM), which gives an image of the surface of the cardiac muscle cell at more detailed levels than conventional live microscopy. This enabled the researchers to see fine structures such as minute tubes (t-tubules), which carry electrical signals into the core of the cell. They could also see that the muscle cell surface is badly disrupted in heart failure.

Heart failure is a condition in which the heart is unable to supply adequate blood flow to meet the body's needs. Hormones such as adrenaline, which are activated by the body in an attempt to stimulate the weak heart, eventually produce further damage and deterioration. There are two types of receptors for adrenaline. The first, beta1AR, strongly stimulates the heart to contract and it can also induce cell damage in the long term. The second, beta2AR, can slightly stimulate contraction but it also has special protective properties.

For the study, the researchers looked at single living cardiac muscle cells in a culture dish, taken from healthy or failing rat hearts. They stimulated the beta1AR and beta2AR receptors using drugs applied via nanopipette inside the t-tubules on the heart muscle cell. They then combined the nano technique SICM with new chemical probes which give fluorescent signals when beta1AR or beta2AR is activated.

They found that the beta2AR receptors are normally anchored in the t-tubules, but in those cells damaged by heart failure they change location and move into the same space as beta1AR receptors. The researchers believe that this altered distribution of receptors might affect the beta2AR receptors' ability to protect cells, and lead to more rapid degeneration of the failing heart.

One of the categories of drugs for slowing the development of heart failure are beta-blockers. They prevent adrenaline from affecting the heart cells by targeting the beta receptors. The new finding increases understanding of what happens to the two receptors in heart failure and could lead to the design of improved beta-blockers. It may eventually help resolve an existing debate about whether it is better to block the beta2AR receptors as well as the beta1AR.